Prevalence of 30-bp deletion variant of latent membrane protein-1 in pediatric transplant patients compared with patients with infectious mononucleosis

Purpose: The focus of this study is the 30-bp deletion variant of the latent membrane protein 1 (LMP1) gene. This variant is thought to be associated with enhanced oncogenic potential and its possible association with posttransplant lymphoproliferative disorder (PTLD) is of interest. As a first step toward exploring its association with viral load dynamics or post-transplant lymphoproliferation, we examined its frequency among transplant patients and patients with infectious mononucleosis (IM) and compared this frequency with the expected frequency based on the literature. Methods: The study samples evaluated were randomly selected from samples obtained from cohorts of transplant patients with varying degrees of EBV DNAemia post-transplant and immunocompetent patients with IM. Subjects with IM were confirmed by EBV serology, which included antibodies to viral capsid antigen (VCA IgM). Total genomic DNA was subject to PCR amplification of the LMP1 gene. Following amplification, sequencing of the LMP1 gene was performed using Sanger sequencing methodology. Results: We sequenced samples from 67 patients; 33 with IM and 34 transplant patients. The median age of transplant patients was 2.8 yrs (range 0.62-16.5), while that of patients with IM was 15.9 yrs (range 2.3-24.2). The 30-bp deletion variant was detected in 2 of 34 transplant samples, including 1 sample from a patient with PTLD, while the sequencing of 33 IM samples yielded one deleted variant. This indicates rates of 5.9% and 3% for transplant and IM patients, respectively. When compared with the literature, the rates of this variant in previous reports from the North American population were as follows: nasopharyngeal carcinoma 18%, Hodgkin lymphoma 27%, AIDS lymphoma 19%, non-malignant EBV infection in healthy patients 48%. Conclusion: Our results indicate that the 30-bp deletion variant of LMP1 is relatively uncommon in our pediatric transplant patients with EBV infection and adolescent patients with infectious mononucleosis. Thus, its presence is potentially more likely to be relevant and not merely due to background prevalence. This biomarker would therefore seem to be a good candidate to investigate for correlation with patient outcomes.